Q99717 (SMAD5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mothers against decapentaplegic homolog 5
Short name=MAD homolog 5
Short name=Mothers against DPP homolog 5

Alternative name(s):
JV5-1
SMAD family member 5
Short name=SMAD 5
Short name=Smad5
Short name=hSmad5

Gene names

Name:	SMAD5
Synonyms:	MADH5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).
Subunit structure	May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1. Ref.12 Ref.13
Subcellular location	Cytoplasm. Nucleus. Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.
Tissue specificity	Ubiquitous.
Post-translational modification	Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase. Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.
Sequence similarities	Belongs to the dwarfin/SMAD family. Contains 1 MH1 (MAD homology 1) domain. Contains 1 MH2 (MAD homology 2) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding Metal-binding Zinc
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	BMP signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB Mullerian duct regression Inferred from electronic annotation. Source: Compara bone development Inferred from electronic annotation. Source: Compara cardiac muscle contraction Inferred from electronic annotation. Source: Compara cartilage development Inferred from electronic annotation. Source: Compara cellular response to BMP stimulus Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to organic cyclic compound Inferred from electronic annotation. Source: Compara embryonic pattern specification Inferred from sequence or structural similarity. Source: UniProtKB erythrocyte differentiation Inferred from electronic annotation. Source: Compara germ cell development Inferred from electronic annotation. Source: Compara osteoblast fate commitment Inferred from electronic annotation. Source: Compara positive regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Inferred from sequence or structural similarity. Source: BHF-UCL protein phosphorylation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transforming growth factor beta receptor signaling pathway Non-traceable author statement Ref.10. Source: UniProtKB ureteric bud development Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome integral to membrane Non-traceable author statement Ref.11. Source: UniProtKB nucleoplasm Traceable author statement. Source: Reactome transcription factor complex Inferred from electronic annotation. Source: InterPro
Molecular_function	RNA polymerase II core promoter sequence-specific DNA binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: InterPro transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Traceable author statement PubMed 19018011. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.7
	Chain	2 – 465	464	Mothers against decapentaplegic homolog 5		PRO_0000090865
Regions
	Domain	13 – 137	125	MH1
	Domain	271 – 465	195	MH2
	Compositional bias	40 – 46	7	Poly-Lys
Sites
	Metal binding	65	1	Zinc By similarity
	Metal binding	110	1	Zinc By similarity
	Metal binding	122	1	Zinc By similarity
	Metal binding	127	1	Zinc By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylthreonine Ref.7
	Modified residue	463	1	Phosphoserine Ref.16
	Modified residue	465	1	Phosphoserine Ref.16
Experimental info
	Mutagenesis	419	1	G → S: Loss of phosphorylation. Ref.5
	Sequence conflict	175	1	D → H in AAC50791. Ref.1
	Sequence conflict	237	1	N → P in AAC50791. Ref.1
	Sequence conflict	293	1	S → R in AAC50791. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q99717 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 4A1FD7EC7BD06728	FASTA	465	52,258
	10 20 30 40 50 60 MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME ELEKALSSPG 70 80 90 100 110 120 QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS HHELKPLDIC EFPFGSKQKE 130 140 150 160 170 180 VCINPYHYKR VESPVLPPVL VPRHNEFNPQ HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP 190 200 210 220 230 240 NNTPFPLSPN SPYPPSPASS TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP 250 260 270 280 290 300 MDTSNNMIPQ IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT 310 320 330 340 350 360 DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD SSIFVQSRNC 370 380 390 400 410 420 NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF EAVYELTKMC TIRMSFVKGW 430 440 450 460 GAEYHRQDVT STPCWIEIHL HGPLQWLDKV LTQMGSPLNP ISSVS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mad-related genes in the human." Riggins G.J., Thiagalingam S., Rosenblum E., Weinstein C.L., Kern S.E., Hamilton S.R., Willson J.K.V., Markowitz S.D., Kinzler K.W., Vogelstein B.V. Nat. Genet. 13:347-349(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor." Hejlik D.P., Kottickal L.V., Liang H., Fairman J., Davis T., Janecki T., Sexton D., Perry W. III, Tavtigian S.V., Teng D.H., Nagarajan L. Cancer Res. 57:3779-3783(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60." Zavadil J., Brezinova J., Svoboda P., Zemanova Z., Michalova K. Leukemia 11:1187-1192(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors." Gemma A., Hagiwara K., Vincent F., Ke Y., Hancock A.R., Nagashima M., Bennett W.P., Harris C.C. Oncogene 16:951-956(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12." Nishimura R., Kato Y., Chen D., Harris S.E., Mundy G.R., Yoneda T. J. Biol. Chem. 273:1872-1879(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLY-419.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[7]	Bienvenut W.V., Lempens A., Norman J.C. Submitted (OCT-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-16; 34-40; 130-158; 283-306 AND 309-319, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, MASS SPECTROMETRY. Tissue: Ovarian carcinoma.
[8]	"TGF-beta signal transduction." Massague J. Annu. Rev. Biochem. 67:753-791(1998) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[9]	"Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells." Verschueren K., Huylebroeck D. Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[10]	"The Smad pathway." Wrana J.L., Attisano L. Cytokine Growth Factor Rev. 11:5-13(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[11]	"TGF-beta signaling by Smad proteins." Miyazono K. Cytokine Growth Factor Rev. 11:15-22(2000) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression." Frontelo P., Leader J.E., Yoo N., Potocki A.C., Crawford M., Kulik M., Lechleider R.J. Oncogene 23:5242-5251(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUV39H1 AND SUV39H2.
[13]	"The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines." Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K. J. Biol. Chem. 280:15992-16001(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LEMD3.
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[16]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-465, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U59913 mRNA. Translation: AAC50791.1. AF010601 mRNA. Translation: AAB66353.1. AF010607 , AF010602, AF010603, AF010604, AF010605, AF010606 Genomic DNA. Translation: AAB92396.1. U73825 mRNA. Translation: AAB95090.1. AF009744 , AF009739, AF009740, AF009741, AF009742, AF009743 Genomic DNA. Translation: AAB82655.1. AF009678 mRNA. Translation: AAB72180.1. BC009682 mRNA. Translation: AAH09682.1.
IPI	IPI00017730.
RefSeq	NP_001001419.1. NM_001001419.1. NP_001001420.1. NM_001001420.1. NP_005894.3. NM_005903.5.
UniGene	Hs.167700.
3D structure databases
ProteinModelPortal	Q99717.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-57571N.
IntAct	Q99717. 1 interaction.
MINT	MINT-1180224.
STRING	9606.ENSP00000384803.
PTM databases
PhosphoSite	Q99717.
Polymorphism databases
DMDM	13959566.
Proteomic databases
PaxDb	Q99717.
PRIDE	Q99717.
Protocols and materials databases
DNASU	4090.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	4090.
KEGG	hsa:4090.
UCSC	uc003lbj.1. human.
Organism-specific databases
CTD	4090.
GeneCards	GC05P135496.
HGNC	HGNC:6771. SMAD5.
MIM	603110. gene.
neXtProt	NX_Q99717.
PharmGKB	PA30528.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG330956.
HOVERGEN	HBG053353.
InParanoid	Q99717.
KO	K16790.
OrthoDB	EOG4HDSTH.
Enzyme and pathway databases
Pathway_Interaction_DB	bmppathway. BMP receptor signaling.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q99717.
Bgee	Q99717.
CleanEx	HS_SMAD5.
Genevestigator	Q99717.
GermOnline	ENSG00000113658. Homo sapiens.
Family and domain databases
Gene3D	2.60.200.10. 1 hit. 3.90.520.10. 1 hit.
InterPro	IPR013790. Dwarfin. IPR003619. MAD_homology1_Dwarfin-type. IPR013019. MAD_homology_MH1. IPR017855. SMAD_dom-like. IPR001132. SMAD_dom_Dwarfin-type. IPR008984. SMAD_FHA_domain. [Graphical view]
PANTHER	PTHR13703. PTHR13703. 1 hit.
Pfam	PF03165. MH1. 1 hit. PF03166. MH2. 1 hit. [Graphical view]
SMART	SM00523. DWA. 1 hit. SM00524. DWB. 1 hit. [Graphical view]
SUPFAM	SSF56366. MAD_MH1. 1 hit. SSF49879. SMAD_FHA. 1 hit.
PROSITE	PS51075. MH1. 1 hit. PS51076. MH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4090.
NextBio	16034.
SOURCE	Search...

Entry information

Entry name

SMAD5_HUMAN

Accession

Primary (citable) accession number: Q99717
Secondary accession number(s): O14688, Q15798, Q9UQA1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 4, 2001
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 142 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.